Although axonal pathology is recognized as one of the major pathological
features of multiple sclerosis, it is less clear how early in its course
it occurs and how it correlates with MRI-visible lesion loads.

To assess
this early axonal pathology, we quantified the concentration of whole-brain
N-acetylaspartate (WBNAA) in a group of patients at the earliest clinical
stage of the disease and compared the results with those from healthy controls.

Conventional brain MRI and WBNAA using unlocalized proton magnetic resonance
spectroscopy were obtained from 31 patients at presentation with clinically
isolated syndromes suggestive of multiple sclerosis and paraclinical evidence
of dissemination in space, and from 16 matched controls.

An additional
conventional MRI scan was obtained in all patients 4-6 months later to
detect dissemination of lesions in time.

The mean WBNAA concentration was
significantly lower in patients compared with the controls (P < 0.0001).

It was not significantly different between patients with and without enhancing
lesions at the baseline MRI or between patients with and without lesion
dissemination in time.

No correlation was found between WBNAA concentrations
and lesion volumes.

Widespread axonal pathology, largely independent of
MRI-visible inflammation and too extensive to be completely reversible,
occurs in patients even at the earliest clinical stage of multiple sclerosis.

This finding lessens the validity of the current concept that the axonal
pathology of multiple sclerosis is the end-stage result of repeated inflammatory
events, and argues strongly in favour of early neuroprotective intervention.